Microtubules, dynamic protein polymers composed of α-tubulin and β-tubulin heterodimers, are a well-established cellular target for anti-cancer drugs. Dynamic polymerization and depolymerization of tubulin heterodimers is a necessary and tightly controlled process during mitosis. Perturbing microtubule dynamics with small molecules blocks the cell cycle in the metaphase/anaphase transition and leads to apoptosis. Therefore, molecules that target tubulin may be used to halt the uncontrolled cell division that characterizes cancer cells. This therapeutic strategy was validated by the success of antimitotic drugs such as paclitaxel, docetaxel, vincristine, and vinblastine, but the clinical utility of these drugs is limited by neurotoxicity and p-glycoprotein-mediated drug resistance. Synthetic taxanes, vinca alkaloid analogs, and novel chemotypes that modulate microtubule dynamics have been synthesized in an attempt to overcome these limitations, but few have produced useful results during clinical trials.